BR122019027913B1 - Partícula vírus-like, composição farmacêutica compreendendo a referida partícula e método para produção da mesma - Google Patents
Partícula vírus-like, composição farmacêutica compreendendo a referida partícula e método para produção da mesma Download PDFInfo
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US8822663B2 (en) | 2010-08-06 | 2014-09-02 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
HUE058896T2 (hu) | 2010-10-01 | 2022-09-28 | Modernatx Inc | N1-metil-pszeudo-uracilt tartalmazó ribonukleinsavak és azok felhasználásai |
US8710200B2 (en) | 2011-03-31 | 2014-04-29 | Moderna Therapeutics, Inc. | Engineered nucleic acids encoding a modified erythropoietin and their expression |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
RS62993B1 (sr) | 2011-10-03 | 2022-03-31 | Modernatx Inc | Modifikovani nukleozidi, nukleotidi, i nukleinske kiseline, i njihove upotrebe |
US9777043B2 (en) | 2011-11-11 | 2017-10-03 | Variation Biotechnologies Inc. | Compositions and methods for treatment of cytomegalovirus |
CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
CA2867789C (en) * | 2012-03-27 | 2022-06-14 | Variation Biotechnologies Inc. | Methods for detection of anti-cytomegalovirus neutralizing antibodies |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
US9303079B2 (en) | 2012-04-02 | 2016-04-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
EP3269388A1 (en) * | 2012-10-30 | 2018-01-17 | Pfizer Inc. | Recombinant particle based vaccines against human cytomegalovirus infection |
EP4074834A1 (en) | 2012-11-26 | 2022-10-19 | ModernaTX, Inc. | Terminally modified rna |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
MX2016004249A (es) | 2013-10-03 | 2016-11-08 | Moderna Therapeutics Inc | Polinulcleotidos que codifican el receptor de lipoproteina de baja densidad. |
EP3158058B1 (en) | 2014-06-18 | 2019-04-17 | MorphoSys AG | Fusion proteins and uses thereof |
KR101678740B1 (ko) * | 2014-10-24 | 2016-11-23 | 단국대학교 천안캠퍼스 산학협력단 | 세포 부착활성 및 골분화 촉진활성을 나타내는 피브로넥틴 융합단백질 |
WO2016149426A1 (en) * | 2015-03-16 | 2016-09-22 | The Broad Institute, Inc. | Constructs for continuous monitoring of live cells |
WO2017068077A1 (en) * | 2015-10-20 | 2017-04-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Methods and products for genetic engineering |
CA3002922A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Human cytomegalovirus vaccine |
US10611800B2 (en) | 2016-03-11 | 2020-04-07 | Pfizer Inc. | Human cytomegalovirus gB polypeptide |
WO2017162265A1 (en) * | 2016-03-21 | 2017-09-28 | Biontech Rna Pharmaceuticals Gmbh | Trans-replicating rna |
MA46584A (fr) * | 2016-10-21 | 2019-08-28 | Modernatx Inc | Vaccin contre le cytomégalovirus humain |
US20210047626A1 (en) * | 2018-04-24 | 2021-02-18 | Merck Sharp & Dohme Corp. | Scalable chromatography process for purification of human cytomegalovirus |
EP3787676A2 (en) * | 2018-05-04 | 2021-03-10 | Spybiotech Limited | Vaccine composition |
US11629172B2 (en) | 2018-12-21 | 2023-04-18 | Pfizer Inc. | Human cytomegalovirus gB polypeptide |
KR20220038608A (ko) * | 2019-05-31 | 2022-03-29 | 배리에이션 바이오테크놀로지스 아이엔씨. | 다형성 교모세포종의 치료를 위한 면역치료 조성물 |
US20210069321A1 (en) | 2019-09-09 | 2021-03-11 | Glaxosmithkline Biologicals Sa | Immunotherapeutic compositions |
US11857622B2 (en) | 2020-06-21 | 2024-01-02 | Pfizer Inc. | Human cytomegalovirus GB polypeptide |
US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
CN115948468A (zh) * | 2022-09-09 | 2023-04-11 | 青岛大学 | 一种人巨细胞病毒重组载体及其制备方法和应用 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6267965B1 (en) | 1981-12-24 | 2001-07-31 | Virogenetics Corporation | Recombinant poxvirus—cytomegalovirus compositions and uses |
JPS61103895A (ja) * | 1984-10-26 | 1986-05-22 | Green Cross Corp:The | HBsAgの精製方法 |
ATE246244T1 (de) | 1988-01-29 | 2003-08-15 | Aventis Pasteur | Rekombinante cmv-neutralisierungsproteine |
US5500161A (en) | 1993-09-21 | 1996-03-19 | Massachusetts Institute Of Technology And Virus Research Institute | Method for making hydrophobic polymeric microparticles |
DE19856463B4 (de) * | 1998-11-26 | 2006-02-02 | Heinrich-Pette-Institut | Retrovirale, mit LCMV pseudotypisierte Hybrid-Vektoren |
DE19910044A1 (de) | 1999-03-08 | 2000-09-14 | Bodo Plachter | Virale Partikel, die nach Infektion durch humanes Cytomegalovirus freigesetzt werden und ihre Verwendung als Impfstoff |
DE60031874D1 (de) * | 1999-09-30 | 2006-12-28 | Univ Washington | Immunologisch relevante antigene aus herpes simplexvirus |
EP1201750A1 (en) * | 2000-10-26 | 2002-05-02 | Genopoietic | Synthetic viruses and uses thereof |
US9045727B2 (en) * | 2002-05-17 | 2015-06-02 | Emory University | Virus-like particles, methods of preparation, and immunogenic compositions |
EP1587816B1 (en) | 2002-12-23 | 2010-06-16 | Vical Incorporated | Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection |
EP1651666B1 (en) | 2003-07-11 | 2009-05-27 | Alphavax, Inc. | Alphavirus-based cytomegalovirus vaccines |
RU2290204C1 (ru) * | 2005-07-27 | 2006-12-27 | Общество с ограниченной ответственностью "Аванген" | Рекомбинантный гибридный белок, препарат для иммунотерапии на его основе и способ иммунотерапии рецидивирующего папилломатоза гортани |
CA2657955A1 (en) * | 2006-07-27 | 2008-08-07 | Ligocyte Pharmaceuticals, Inc. | Chimeric virus-like particles |
US20090123494A1 (en) * | 2007-07-31 | 2009-05-14 | William Staplin | Momlv-based pseudovirion packaging cell line |
US20110250675A1 (en) | 2008-03-26 | 2011-10-13 | Life Technologies Corporaiton | Virus-Like Particle Mediated Cellular Delivery |
GB0907935D0 (en) * | 2009-05-08 | 2009-06-24 | Henderson Morley Plc | Vaccines |
US9777043B2 (en) | 2011-11-11 | 2017-10-03 | Variation Biotechnologies Inc. | Compositions and methods for treatment of cytomegalovirus |
US9907844B2 (en) * | 2013-12-11 | 2018-03-06 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Human herpesvirus trimeric glycoprotein B, protein complexes comprising trimeric gB and their use as vaccines |
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